Safety Study of TRx0237 in Patients Already Taking Medications for Mild and Moderate Alzheimer's Disease

This study has been terminated.
(This study has been terminated for administrative reasons only.)
Sponsor:
Information provided by (Responsible Party):
TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier:
NCT01626391
First received: June 20, 2012
Last updated: April 18, 2013
Last verified: April 2013
  Purpose

The primary purpose of this study is to assess the safety and tolerability of TRx0237 when taken at the same time as acetylcholinesterase inhibitors (i.e., donepezil, galantamine, or rivastigmine) and / or memantine to treat patients with mild to moderate Alzheimer's Disease.


Condition Intervention Phase
Alzheimer's Disease
Drug: TRx0237
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled, Randomised, 4-Week Safety and Tolerability Study of TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease on Pre-Existing Stable Acetylcholinesterase Inhibitor and/or Memantine Therapy

Resource links provided by NLM:


Further study details as provided by TauRx Therapeutics Ltd:

Primary Outcome Measures:
  • Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Safety parameters included adverse events, vital signs, methemoglobin, physical and neurological examinations, laboratory tests (hematology, serum chemistry, urinalysis, and troponin), electrocardiograms, assessment of serotonin syndrome, and potential for suicidal behaviour and thoughts.


Other Outcome Measures:
  • Effect of TRx0237 on monoamine oxidase activity [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: September 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRx0237 Drug: TRx0237
TRx0237 tablets 250 mg/day (given as 125 mg bid) for 4 weeks
Placebo Comparator: Placebo Drug: Placebo
Placebo tablets will be administered twice daily (b.i.d.) for 4 weeks. The placebo tablets include 4 mg of TRx0237 as a urinary and faecal colourant to maintain blinding; hence, the placebo group will receive a total of 8 mg/day of TRx0237.

  Eligibility

Ages Eligible for Study:   up to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Clinical diagnosis of all cause dementia and probable Alzheimer's disease (AD)
  • Mini-Mental State Examination (MMSE) score of 14-26 (inclusive)
  • Cognitive impairment present for at least 6 months
  • Age ≤90 years
  • Modified Hachinski ischaemic score of ≤4
  • Females, if of childbearing potential, must use adequate contraception and maintain this use throughout participation in the study
  • Patient is able to read, understand, and provide written informed consent
  • Has one or more identified caregivers who are able to verify daily compliance with study drug and provide information on safety and tolerability; the caregiver(s) must also give consent to participate
  • Currently taking an taking an acetylcholinesterase inhibitor and/or memantine; the subject must have been taking such medication(s) for ≥3 months. The dosage regimen must have remained stable for ≥6 weeks and it must be planned to remain stable throughout participation in the study.
  • Able to comply with the study procedures

Exclusion Criteria:

  • Significant central nervous system disorder other than Alzheimer's disease
  • Patients in whom baseline MRI is contraindicated such as metal implants in head (except dental), pacemaker, and cochlear implant
  • Significant focal or intracranial pathology that would lead to a diagnosis other than probable Alzheimer's disease
  • Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness
  • Epilepsy
  • Major depressive disorder, schizophrenia or other psychotic disorders, bipolar disorder, substance (including alcohol) related disorders
  • Resides in a hospital or continuous care facility
  • History of swallowing difficulties
  • Pregnant or breastfeeding
  • History of significant hematological abnormality or current acute or chronic clinically significant abnormality
  • Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator
  • Clinically significant cardiovascular disease or abnormal assessments
  • Pre-existing or current signs or symptoms of respiratory failure
  • Concurrent acute or chronic clinically significant immunologic, renal, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than Alzheimer's disease
  • Prior intolerance to methylthioninium-containing drug or any of the excipients
  • Treatment currently or within 3 months before Baseline with any of the following medications (unless otherwise noted):

    • Tacrine
    • Anxiolytics and/or sedatives/hypnotics (exceptions: sedation for MRI or occasional short-acting benzodiazepines, chloral hydrate, or zolpidem as needed at bedtime)
    • Antipsychotics (clozapine, chlorpromazine, thioridazine, or ziprasidone)
    • Carbamazepine
    • Drugs associated with methaemoglobinaemia (e.g., dapsone, local anesthetics such as benzocaine used chronically, primaquine and related antimalarials, sulfonamides)
    • Warfarin (and other Coumadin derivates such as phenprocoumon)
  • Current or prior participation in a clinical trial of a drug, biologic, or device in which the last dose was received within 28 days prior to Baseline
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01626391

Locations
Germany
Achim, Germany
Berlin, Germany
Leipzig, Germany
München, Germany
United Kingdom
Birmingham, United Kingdom
Bradford, United Kingdom
Crowborough, United Kingdom
Duston, United Kingdom
Oxford, United Kingdom
Sheffield, United Kingdom
St Leonards on Sea, United Kingdom
Staffordshire, United Kingdom
Sponsors and Collaborators
TauRx Therapeutics Ltd
Investigators
Principal Investigator: Mark Dale, MD MAC Clinical Research
  More Information

No publications provided

Responsible Party: TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier: NCT01626391     History of Changes
Other Study ID Numbers: TRx-237-008
Study First Received: June 20, 2012
Last Updated: April 18, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by TauRx Therapeutics Ltd:
Alzheimer's Disease
TRx0237
Safety Study
AD

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014